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Pembrolizumab Combined With Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Oesophageal Squamous Cell Carcinoma: Protocol for a Multicentre, Prospective, Randomized-Controlled, Phase III Clinical Study (Keystone-002)
BACKGROUND: To compare the efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy (neoCT) versus neoadjuvant chemoradiotherapy (neoCRT) followed by surgery for locally advanced resectable oesophageal squamous cell carcinoma (ESCC). METHODS: This study is a multicentre, prospecti...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008846/ https://www.ncbi.nlm.nih.gov/pubmed/35433421 http://dx.doi.org/10.3389/fonc.2022.831345 |
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author | Shang, Xiaobin Zhang, Wencheng Zhao, Gang Liang, Fei Zhang, Chen Yue, Jie Duan, Xiaofeng Ma, Zhao Chen, Chuangui Pang, Qingsong Zhang, Weihong Liu, Liang Ren, Xiubao Meng, Bin Zhang, Peng Ma, Yegang Zhang, Lin Li, Hecheng Kang, Xiaozheng Li, Yin Jiang, Hongjing |
author_facet | Shang, Xiaobin Zhang, Wencheng Zhao, Gang Liang, Fei Zhang, Chen Yue, Jie Duan, Xiaofeng Ma, Zhao Chen, Chuangui Pang, Qingsong Zhang, Weihong Liu, Liang Ren, Xiubao Meng, Bin Zhang, Peng Ma, Yegang Zhang, Lin Li, Hecheng Kang, Xiaozheng Li, Yin Jiang, Hongjing |
author_sort | Shang, Xiaobin |
collection | PubMed |
description | BACKGROUND: To compare the efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy (neoCT) versus neoadjuvant chemoradiotherapy (neoCRT) followed by surgery for locally advanced resectable oesophageal squamous cell carcinoma (ESCC). METHODS: This study is a multicentre, prospective, randomized-controlled, phase III clinical study. Eligible ESCC (staging: cT1N2M0 or cT2-3N0-2M0 (stage II/III, high-risk lesions in T2N0M0)) patients will be randomly assigned to either the experimental group (pembrolizumab with neoCT, n = 228) or the control group (neoCRT, n = 114) at a ratio of 2:1. Within 4–6 weeks after preoperative therapy, the McKeown procedure will be performed. Patients in the experimental group will also receive pembrolizumab alone as adjuvant therapy after surgery until 1 year or until the radiographically confirmed PD or other condition indicated for premature termination is observed. The primary endpoint is event-free survival (EFS). The secondary endpoints are 1-, 3-, and 5-year overall survival (OS) and disease-free survival (DFS), short-term outcomes, and quality of life. DISCUSSION: This is the first prospectively randomized controlled trial designed to compare pembrolizumab plus chemotherapy and chemoradiotherapy as neoadjuvant therapy for resectable ESCC. According to our hypothesis, preoperative pembrolizumab combined with chemotherapy will result in a better tumour response and prolong the survival of patients, with acceptable toxicity. This study started in December 2021, and the enrolment time is estimated to be 2 years. TRIAL REGISTRATION: This prospective study has been registered at ClinicalTrials.gov (NCT04807673), March 2021. |
format | Online Article Text |
id | pubmed-9008846 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90088462022-04-15 Pembrolizumab Combined With Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Oesophageal Squamous Cell Carcinoma: Protocol for a Multicentre, Prospective, Randomized-Controlled, Phase III Clinical Study (Keystone-002) Shang, Xiaobin Zhang, Wencheng Zhao, Gang Liang, Fei Zhang, Chen Yue, Jie Duan, Xiaofeng Ma, Zhao Chen, Chuangui Pang, Qingsong Zhang, Weihong Liu, Liang Ren, Xiubao Meng, Bin Zhang, Peng Ma, Yegang Zhang, Lin Li, Hecheng Kang, Xiaozheng Li, Yin Jiang, Hongjing Front Oncol Oncology BACKGROUND: To compare the efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy (neoCT) versus neoadjuvant chemoradiotherapy (neoCRT) followed by surgery for locally advanced resectable oesophageal squamous cell carcinoma (ESCC). METHODS: This study is a multicentre, prospective, randomized-controlled, phase III clinical study. Eligible ESCC (staging: cT1N2M0 or cT2-3N0-2M0 (stage II/III, high-risk lesions in T2N0M0)) patients will be randomly assigned to either the experimental group (pembrolizumab with neoCT, n = 228) or the control group (neoCRT, n = 114) at a ratio of 2:1. Within 4–6 weeks after preoperative therapy, the McKeown procedure will be performed. Patients in the experimental group will also receive pembrolizumab alone as adjuvant therapy after surgery until 1 year or until the radiographically confirmed PD or other condition indicated for premature termination is observed. The primary endpoint is event-free survival (EFS). The secondary endpoints are 1-, 3-, and 5-year overall survival (OS) and disease-free survival (DFS), short-term outcomes, and quality of life. DISCUSSION: This is the first prospectively randomized controlled trial designed to compare pembrolizumab plus chemotherapy and chemoradiotherapy as neoadjuvant therapy for resectable ESCC. According to our hypothesis, preoperative pembrolizumab combined with chemotherapy will result in a better tumour response and prolong the survival of patients, with acceptable toxicity. This study started in December 2021, and the enrolment time is estimated to be 2 years. TRIAL REGISTRATION: This prospective study has been registered at ClinicalTrials.gov (NCT04807673), March 2021. Frontiers Media S.A. 2022-03-31 /pmc/articles/PMC9008846/ /pubmed/35433421 http://dx.doi.org/10.3389/fonc.2022.831345 Text en Copyright © 2022 Shang, Zhang, Zhao, Liang, Zhang, Yue, Duan, Ma, Chen, Pang, Zhang, Liu, Ren, Meng, Zhang, Ma, Zhang, Li, Kang, Li and Jiang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Shang, Xiaobin Zhang, Wencheng Zhao, Gang Liang, Fei Zhang, Chen Yue, Jie Duan, Xiaofeng Ma, Zhao Chen, Chuangui Pang, Qingsong Zhang, Weihong Liu, Liang Ren, Xiubao Meng, Bin Zhang, Peng Ma, Yegang Zhang, Lin Li, Hecheng Kang, Xiaozheng Li, Yin Jiang, Hongjing Pembrolizumab Combined With Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Oesophageal Squamous Cell Carcinoma: Protocol for a Multicentre, Prospective, Randomized-Controlled, Phase III Clinical Study (Keystone-002) |
title | Pembrolizumab Combined With Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Oesophageal Squamous Cell Carcinoma: Protocol for a Multicentre, Prospective, Randomized-Controlled, Phase III Clinical Study (Keystone-002) |
title_full | Pembrolizumab Combined With Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Oesophageal Squamous Cell Carcinoma: Protocol for a Multicentre, Prospective, Randomized-Controlled, Phase III Clinical Study (Keystone-002) |
title_fullStr | Pembrolizumab Combined With Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Oesophageal Squamous Cell Carcinoma: Protocol for a Multicentre, Prospective, Randomized-Controlled, Phase III Clinical Study (Keystone-002) |
title_full_unstemmed | Pembrolizumab Combined With Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Oesophageal Squamous Cell Carcinoma: Protocol for a Multicentre, Prospective, Randomized-Controlled, Phase III Clinical Study (Keystone-002) |
title_short | Pembrolizumab Combined With Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Oesophageal Squamous Cell Carcinoma: Protocol for a Multicentre, Prospective, Randomized-Controlled, Phase III Clinical Study (Keystone-002) |
title_sort | pembrolizumab combined with neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy followed by surgery for locally advanced oesophageal squamous cell carcinoma: protocol for a multicentre, prospective, randomized-controlled, phase iii clinical study (keystone-002) |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008846/ https://www.ncbi.nlm.nih.gov/pubmed/35433421 http://dx.doi.org/10.3389/fonc.2022.831345 |
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